International Immunology, Vol. 14, No. 8, pp. 917-924,
August 2002
© 2002 Japanese Society for Immunology
Increased IL-15 production of muscle cells in polymyositis and dermatomyositis
1 Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan
Correspondence to: T. Sugiura; E-mail: tsugiura{at}ior.twmu.ac.jp
Transmitting editor: T. Watanabe
In polymyositis (PM)/dermatomyositis (DM), various cytokines, especially macrophage-derived cytokines such as IL-1
, IL-1ß and tumor necrosis factor (TNF)-, are expressed in the inflammatory foci. We previously reported that IL-15, a novel cytokine with a biological activity similar to that of IL-2, is expressed in muscle cells in PM/DM. In the present study, we set out to investigate the regulation of IL-15 in cultured myoblasts. Myoblasts constitutively produced a low level of IL-15 and the production was augmented by stimulation with IFN-
, IL-1, IL-1ß, TNF- or lipopolysaccharide (LPS) in a dose-dependent manner. These stimuli also enhanced the expression of IL-15 mRNA. About 30–40% of IL-15 was detected intracellularly, while the rest was released into the culture supernatant. Immunohistochemical staining revealed that intracellular IL-15 was localized in the perinuclear area of the cytoplasm in the myoblasts. Despite the considerable amounts of intracellular IL-15, the myoblasts predominantly expressed authentic IL-15 mRNA isoform. This isoform generates IL-15 with long signal peptide preprotein, which is all to be secreted. The biological activity of IL-15 secreted from the myoblasts was examined using an IL-15-dependent murine T cell line, CTLL-2. Culture supernatants of the myoblasts induced a proliferative response of CTLL-2 and this was specifically inhibited by anti-IL-15 antibody. These results suggest that inflammatory stimuli induce the production of IL-15 in the muscle cells in PM/DM, and IL-15 may contribute to the immunopathogenesis by augmenting recruitment and activation of the infiltrating T cells. Blocking of IL-15 production might be of therapeutic value in PM/DM.
Keywords: dermatomyositis, IL-15, muscle cells, polymyositis
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